The brain is a rich source of adenylate cyclase and phosphodiesterase, and the turnover of cyclic AMP there is rapid. Increasing evidence indicates that cyclic AMP is critically involved in neuronal function. The hydrolysis of cyclic AMP to 5'-AMP by phosphodiesterase is the only known mechanism by which the action of cyclic AMP is terminated. Studies of phosphodiesterase thus assume significance. We will continue to characterize phosphodiesterase(s) and its activator. Future work will include (1) purification and characterization of the activator-dependent and activator-independent forms of phosphodiesterase; (2) characterization of the multiple molecular forms of phosphodiesterases and their interconversion; (3) preparation of antibodies against phosphodiesterase and its activator; (4) subcellular localization of the enzyme and activator in tissues using immunofluorescence techniques; (5) elucidation of the mechanism of activation of phosphodiesterase by the activator and by trypsin; (6) elucidation of the mechanism of activation of brain adenylate cyclase by the protein activator.